DESCRIPTION: The c-Myc proto-oncogene encodes a multifunctional nuclear protein that is required, and in some cases, sufficient, for cellular proliferation. Deregulation of its expression is associated with the development of diverse types of tumors. However, it has recently been shown that overexpression of Myc in conjunction with growth factor deprivation can elicit programmed cell death. These observations suggest that Myc deregulation in cells may not necessarily elicit an aggressive tumor but instead these cells may be eliminated by apoptosis, unless other lesions that counteract apoptosis are developed. Support for this hypothesis comes from his findings that apoptosis mediated by deregulated Myc expression is blocked either by overexpression of survival genes or by loss of critical components of the apoptotic pathway. The mechanisms by which Myc mediates cell cycle progression and apoptosis are not clear. It is not known if all of Myc's activities are dependent on its ability to regulate transcription. His long term goal is to elucidate the basis for these mechanisms. This proposal is focused on the identification of downstream targets and interacting proteins which are required for and/or modulate the activiites of Myc. He proposes to determine whether Myc-dependent tranactivation is invbolved in the regulation of cell cycle progression and apoptosis, to identify genes that ar either directly induced or suppressed by Myc, and to identify proteins that specifically interact with the amino terminal region of Myc (a region required for cellular proliferation , transformation, transcriptional regulation and apoptosis). He proposes to test the function of the identified proteins in cell growth and apoptosis and in regulating Myc activities.